NIR-II Fluorescent Molecular Bottlebrush Prepared by Ring-Opening Polymerization for Programmed Cell Death Ligand‑1 Checkpoint Imaging

In the area of tumor therapy, the immune checkpoint drugs programmed death-1 receptor (PD-1) and programmed death-ligand 1 (PD-L1) have been widely used in clinical trials and shown excellent therapeutic effects. The PD-L1 expression on cancer cells can be considered the predictive biomarker for patients, and the second near-infrared (NIR-II) window fluorescence imaging is ideal for immune checkpoint research. Conjugated polymers, as a kind of organic semiconductor, have very extensively applications in NIR-II fluorescence imaging, but the biological application is limited with the poor water solubility. Here, we developed a brush-on-brush molecular bottlebrush through a two-step “grafting from” strategy by ring-opening polymerization (ROP). Then, a PD-L1 monoclonal antibody (mAb) was conjugated with a molecular bottlebrush to afford the fluorophore (anti-PD-L1)-P­(TTQ-F)-g-(PLL₃₀-g-(PGA)₅) specific to the PD-L1 checkpoint. The fluorophore exhibits strong NIR-II fluorescence signals and selective targeting ability of PD-L1. Moreover, after an intravenous injection of (anti-PD-L1)-P­(TTQ-F)-g-(PLL₃₀-g-(PGA)₅) into the BALB/c mice bearing CT26 tumors, the tumor-to-normal tissue (T/NT) signal ratio sharply increased with a maximum T/NT = 11.90 at 12 h p.i. during the initial 12 h post-injection. This study provides bright future outlooks for immune checkpoint imaging and further immunotherapy.